AMBER Archive (2004)

Subject: Re: AMBER: MM-PBSA: molecular charges and active site water

From: ML (
Date: Fri Feb 13 2004 - 01:30:23 CST

Dear Anselm,
another article comparing differences between using MM-PBSA and some
explicit waters is Kuhn B & Kollman PA, 2000, J AM Chem Soc, 122,
3909-3916. They found that two explicit
waters make the correlation with experiment better.

Best regards,

Martin Lepsik

David A. Case wrote:

>On Thu, Feb 12, 2004, Anselm Horn wrote:
>>Is the total charge of the system of crucial importance for MM-PBSA
>>calculations, i.e. should both ligand and receptor be electrically neutral?
>>Is there a problem, if the ligand and receptor have the same charge but
>>opposite sign? However, counterions, when added to the complex, are to be
>>excluded from the ligand/receptor definition in in any case.
>There is no requirement in principle that the ligand or receptor be neutral.
>But which charged interactions, is can be difficult to get a good balance
>between solvent screening and the direct interactions, if for no other reason
>that the "raw" interactions are so much larger than for uncharged systems.
>>My system contains some active site water molecules that are hidden from
>>the rest of the solvent by the ligand/receptor environment. How do I
>>include those in the MM-PBSA calculation? Is it feasable to make them
>>belong to the receptor or do I have to treat the other case as well, where
>>they belong to the ligand?
>I don't know of any real research that answers this question; handling of
>"bound" waters can be a real headache for mm-pbsa calculations.
>A couple of (my) papers that deal with these problems are the following:
> V. Tsui
>%A D.A. Case
>%T Calculations of the Absolute Free Energies of Binding between RNA and Metal
>%Ions Using Molecular Dynamics Simulations and Continuum Electrostatics
>%J J. Phys. Chem. B
>%V 105
>%P 11314-11325
>%D 2001
>%A H. Gohlke
>%A D.A. Case
>%T Converging Free Energy Estimates: MM-PB(GB)SA Studies on the
>%Protein-Protein Complex Ras-Raf
>%J J. Comput. Chem.
>%V 25
>%P 238-250
>%D 2004
>...good luck...dac

Martin Lepsik
Dept. of Molecular Modeling
Institute of Organic Chemistry & Biochemistry
Czech Academy of Sciences
phone: +420-220 183 540
fax:+420-220 183 292

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